Synthesis of Iriomoteolide-1a C13-C23 Fragment via Asymmetric Conjugate Addition and Julia-Kocienski Coupling Reaction

The key C13-C23 fragment toward the total synthesis of irlomoteolide-1a (1) has been constructed from an 1,2-acetonide containing aldehyde 5 via a Julia-Kocienski olefination with the C16-C23 segment 6. The key step involves stereoselective introduction of the C29 methyl group by a highly efficient Cul-Tol-BINAP-catalyzed asymmetric conjugate addition of methylmagnesium bromide to an alpha,beta-unsaturated ester.